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Essential Oils and Bioactive Components Against Arthritis: a Novel Perspective on Their Therapeutic Potential

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Essential Oils and Bioactive Components Against Arthritis: a Novel Perspective on Their Therapeutic Potential plants Review Essential Oils and Bioactive Components against Arthritis: A Novel Perspective on Their Therapeutic Potential Mariangela Marrelli * , Valentina Amodeo, Maria Rosaria Perri, Filomena Conforti y and Giancarlo Statti y Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy; [email protected] (V.A.); [email protected] (M.R.P.); fi[email protected] (F.C.); [email protected] (G.S.) * Correspondence: [email protected]; Tel.: +39-0984-493168; Fax: +39-0984-493107 These authors jointly supervised and contributed equally to this work. y Received: 18 August 2020; Accepted: 21 September 2020; Published: 23 September 2020 Abstract: Essential oils (EOs) are known to possess a number of beneficial properties. Their antimicrobial, anti-inflammatory, antioxidant, antidiabetic, and cancer-preventing activities have been extensively reported. Due to their wide use as food preservers and additives, as well as their use in agriculture, perfumes, and make-up products, these complex mixtures of volatile compounds have gained importance from a commercial point of view, not only in the pharmaceutical industry, but also in agronomic, food, cosmetic, and perfume industries. An analysis of the recent scientific literature allowed us to highlight the presence of an increasing number of studies on the potential antiarthritic properties of EOs and their main constituents, which seems to suggest a new interesting potential therapeutic application. The aim of this review is to examine the current knowledge on the beneficial effects of essential oils in the treatment of arthritic diseases, providing an overview of the reports on the in vivo and in vitro effects of EOs. Furthermore, this review critically examines the recent findings on the potential roles of the main components of EOs in the exerted beneficial effects. Obtained negative results are also reported. Keywords: anti-arthritic; anti-inflammatory; essential oils; medicinal plants; rheumatoid arthritis; secondary metabolites; terpenes 1. Introduction Arthritis is one of the most common chronic health problems and a major cause of disability [1]. The term “arthritis” derives from the Greek words “arthron” and “ites”, which mean inflammation of the joint. It can be defined as a chronic, inflammatory, and systemic autoimmune disorder characterized by pain, swelling, and rigidity of the synovial joints [2]. Arthritis includes more than 100 different disorders, with osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis, gout, and fibromyalgia being the most common types [3]. Osteoarthritis is the most frequent form of arthritis [4]. This degenerative disease is characterized by damage to the articular cartilage of the knee, hip, and others lower extremity joints. The estimated risk for knee OA is approximately 47% in women and 40% in men, and its prevalence is projected to increase because of the ageing of the population and the growing occurrence of obesity [5]. Rheumatoid arthritis is a chronic and systemic inflammatory autoimmune disorder in which joint inflammation leads to cartilage and bone damage, disability, and even to systemic complications and enhanced morbidity and mortality [6]. A number of factors, such as genetic factors, the environment, and autoimmunity, Plants 2020, 9, 1252; doi:10.3390/plants9101252 www.mdpi.com/journal/plants Plants 2020, 9, 1252 2 of 17 play roles in RA pathogenesis [7]. All these factors induce the activation of the immune system, which cause autoantigen presentation with antigen-specific T and B cells activation and aberrant inflammatory cytokines production, thus leading to synovitis and cartilage and subchondral bone destruction. Extra-articular organs, such as the skin and the cardiovascular system, can also be involved [6]. The pharmacological management of both these major forms of arthritis is mostly symptomatic and is aimed at reducing pain and inflammation. This includes the use of non-steroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids. Current treatment modalities for RA are based on the use of disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, hydroxychloroquine, and sulfasalazine. However, these drugs can cause serious side effects, including gastrointestinal complaints, pneumonitis, and liver function abnormalities. More recently, biologic drugs (antibodies or soluble receptors for IL-1, IL-6, and TNF-a) have gained importance in the treatment of OA and RA. These agents are able to reduce inflammation and joint destruction, however besides the higher cost of such new agents, which limits their use, both their long-term side effects and benefits have not yet been fully understood. These drugs are not always effective and severe side effects may occur, such as serious infections and increased risk of cancer. Immunosuppressive and cytotoxic drugs (e.g., leflunomide, azathioprine, cyclosporine, and cyclophosphamide) may be used as well, but these drugs also cause a number of toxic side effects [8,9]. As a consequence, the use of botanicals and nutritional supplements has gained importance, and the number of studies on the potential health benefits of plant extracts in the treatment of arthritis is increasing [10]. The antiarthritic potential of plant species and extracts has been extensively reviewed in the last decade, and a number of papers dealing with such botanicals have been published [11–20]. In contrast, the present review aims to specifically offer an overview of the plant essential oils (EOs) with antiarthritic potential. Essential oils are complex mixtures containing low molecular weight compounds, mainly monoterpenes, sesquiterpenes, and oxygenated derivatives, extracted from aromatic plants [21]. A number of biological properties have been detected for EOs, such as antimicrobial, antioxidant, cancer-preventing, antimutagenic, antidiabetic, and anti-inflammatory properties [22–24]. The analysis of the most recent literature allowed us to identify an increasing number of studies focusing on the in vitro and in vivo antiarthritic properties of essential oils. Overall, these findings give interesting perspectives on the therapeutic use of EOs and their chemical constituents. 2. Methods This search, conducted over a period of 5 months, included references published up until July 2020. The academic search engines Google Scholar, Pubmed, Microsoft Academic, and Scopus were utilized. The keywords “essential oils”, “arthritis”, “antiarthritic”, “anti-rheumatoid arthritic effect”, “terpenes”, and “volatile oil” were searched in the databases. These descriptors were combined by using Boolean operators, e.g., “and”, “+”, allowing for more targeted results. Studies focusing on the antiarthritic potential of essential oils in their whole forms or their single pure active components were included in the research, and both in vitro and in vivo studies were taken into account. 3. Essential Oils with Antiarthritic Potential The purpose of this review is to provide an overview of the studies dealing with the potential beneficial effects of EOs and their phytochemical constituents on arthritic conditions. A total of 31 EOs from different plant species have been reported in the literature to have in vitro or in vivo effectiveness. The investigated EOs that have been proved to have antiarthritic potential belong to a number of plant families (Figure1), mainly Lamiaceae (6 species) and Zingiberaceae (5), followed by Cupressaceae, Cyperaceae, Ericaceae, Myrtaceae, and Pinaceae (2). Plants 2020, 9, 1252 3 of 17 Plants 2020, 9, x FOR PEER REVIEW 3 of 19 Figure 1. Number of plant species whose essential oils (EOs) showed antiarthritic potential for the Figure 1. Number of plant species whose essential oils (EOs) showed antiarthritic potential for the different families.different families. 3.1. Aquilaria3.1. agallocha Aquilaria agallochaRoxb. Roxb. Aquilaria agallochaAquilaria agallochaRoxb. Roxb. (Thymelaeaceae), (Thymelaeaceae), commonly commonly known knownas “agarwood”, as “agarwood”, grows wild in the grows wild in Himalayan region and East India, and it is cultivated in India, Bangladesh, Indonesia, and Sri Lanka the Himalayan[25]. Agarwood region and EOs Eastand extracts India, contain andit a iscomplex cultivated mixture in of India,sesquiterpenes Bangladesh, and chromones. Indonesia, and Sri Lanka [25].Depending Agarwood on the EOs extraction and extracts technique, contain fatty acids a and complex phenols mixture have also been of sesquiterpenes identified. A number and chromones. Depending onof biological the extraction properties technique, have been fattyreported acids for th andis species, phenols such have as anti alsooxidant, been antimicrobial, identified. A number of antidiabetic, and antinociceptive properties [26,27]. biological propertiesRahman have and colleagues been reported reported for the this anti-arthtritic species, suchpotential as of antioxidant, A. agallocha Roxb. antimicrobial, heartwood antidiabetic, and antinociceptiveessential oil properties(EO) [28]. In vitro, [26, 27at the]. concentration of 500 µg/mL, this essential oil was demonstrated Rahmanto induce and colleagues56.71% inhibition reported of protein the denaturati anti-arthtriticon. The biological potential potential of A. was agallocha also assessedRoxb. in heartwood vivo, in Freund’s adjuvant-induced arthritic rat model. At doses of 125 mg/kg and 250 mg/kg, A. essential oilagallocha (EO) [ 28EO]. inhibitedIn vitro the, atincrease the concentrationin
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